Approved dosage regimens for prescription drug products are developed with a view to obtaining a favourable therapeutic index in the overall exposed population. The purpose of this study was to ...examine differences between the approved dosage regimen and the clinically prescribed doses of allopurinol in major hospitals in Japan.
The prescribing records for allopurinol were scrutinized at five national hospitals in Japan. Prescription information, including mean dose and the distribution of doses, was extracted for each hospital and the data compared with the dosage recommended in the approved labelling for the product. In addition, therapeutic drug monitoring (TDM) data were examined to evaluate relationships between dose administered, serum concentration of oxypurinol, and clinical efficacy.
The mean dose of allopurinol prescribed in the five institutions, 131.7 mg/day, was lower than the approved dosage of 200-300 mg/day. There were no differences in the mean dose between the hospitals, and similar dose distributions were seen among the hospitals. Approximately 60-70% of patients were treated with 100 mg/day and 20-30% with 200 mg/day of allopurinol. The most frequent dosage of allopurinol used in clinical practice was 100 mg/day. In the TDM study, the mean trough serum concentrations of oxypurinol were 9.5+/-3.6 microg/mL (50 mg/day), 13.0+/-6.8 microg/mL (100 mg/day), 19.8+/-12.9 microg/mL (200 mg/day) and 15.7+/-7.3 microg/mL (300 mg/day). The mean values of creatinine clearance were 17.0+/-16.4 mL/min (50 mg/day), 33.5+/-32.8 mL/min (100 mg/day), 57.8+/-33.8 mL/min (200 mg/day) and 94.3+/-35.8 mL/min (300 mg/day, in patients with normal renal function), and showed a downward trend together with a reduction of dosage of allopurinol. Allopurinol was given to 91% (91/100) of patients at a daily dose of 100-200 mg, and the oxypurinol trough serum concentration attained (>4.6 microg/mL) was sufficient to maintain a therapeutic effect in 92.3% (84/91) of these patients. A daily dose of 100-200 mg may be enough to obtain therapeutic serum oxypurinol concentrations in most Japanese patients.
Dose of 100-300 mg/day was an effective and commonly used dosing regimen for allopurinol in Japanese patients. The approved dosage range (200-300 mg/day) may be too high for patients with renal dysfunction, suggesting the recommended dosing regimen for allopurinol should be revised to include the lower doses.
We present measurements of the spectral distribution of transition radiation generated by electrons of momentum 1–10
GeV/
c in different radiator types. We investigate periodic foil radiators and ...irregular foam and fiber materials. The transition radiation photons are detected by prototypes of the drift chambers to be used in the Transition Radiation Detector (TRD) of the ALICE experiment at CERN, which are filled with a Xe, CO
2 (15%) mixture. The measurements are compared to simulations in order to enhance the quantitative understanding of transition radiation production, in particular the momentum dependence of the transition radiation yield.
Ninety-two consecutive patients with unresectable hepatocellular carcinoma (HCC) greater than 2 cm and less than 5 cm in diameter were treated by transcatheter arterial chemoembolization using ...autologous blood clot as an embolizing agent (Short-TAE; S-TAE). Survival, patency of hepatic arteries and side effects were retrospectively analyzed. The median follow-up interval was 42 months. The median size of the main tumor was 3.4 cm in diameter. All tumors were determined to be inoperable because of intrahepatic spread of tumors and/or poor hepatic functional reserves. S-TAE was performed by injecting a mixture of iodized oil and anticancer drugs followed by embolization of hepatic arteries with autologous blood clot. Embolization with clots maintained patency of hepatic arteries in all the patients. The overall survival rates for 92 HCC patients at 1, 3, 5, 7 and 8 years were estimated by the Kaplan-Meier method to be 100, 52, 34, 12 and 6%, respectively, which were better compared with prior records for conventional method with gelfoam. S-TAE was successfully performed in 16 patients with Childs class C liver cirrhosis presenting icterus and ascitis. The survival rates for Childs class C patients at 1, 2 and 3 years were 100, 66 and 32%, respectively. The Cox proportional hazard model was used to assess influence of each pretreatment parameter (age, gender, virus marker, stage of cirrhosis, number of tumor) on survival. The univariate analysis demonstrated that both the stage of cirrhosis and the multiplicity of tumor were significant factors predicting survival (p=0.003 and 0.046, respectively). The multivariate analysis showed the stage of cirrhosis to be the sole factor which significantly affected prognosis of HCC patients (p=0.005). In conclusion, chemoembolization with autologous blood clot is an effective and safe therapeutic option for unresectable HCC smaller than 5 cm. The hepatic functional reserves play a key role in determining prognosis of HCC patients.
In J-PARC heavy-ion project, we aim at studies of QCD phase structures and hadron properties in high baryon density close to the neutron star core. We have developed a heavy-ion acceleration scheme ...with a new linac and a new booster with existing two synchrotrons with the goal beam rate of about 1011 Hz. We have also designed a large acceptance spectrometer based on a toroidal magnet. We have evaluated the spectrometer performance, and demonstrated reconstructing dielectron and dimuon spectra with full detector simulations. Finally, we designed a hypernuclear spectrometer which can utilize the full intensity ion beams.
We successfully produced Resistive-Electrode GEM (RE-GEM) that was applied Resistive-Kapton to electrodes. We measured the gain curve of RE-GEM using an 55 Fe radioactive source in the gas mixture of ...Ar 70% and CO 2 30%. We obtained the maximum gain of about 300 at an applied voltage of 740 V.
Here, we describe the details of a silicon–tungsten prototype electromagnetic calorimeter module and associated readout electronics. Detector performance for this prototype has been measured in test ...beam experiments at the CERN PS and SPS accelerator facilities in 2015/16. The results are compared to those in Monte Carlo Geant4 simulations. This is the first real-world demonstration of the performance of a custom ASIC designed for fast, lower-power, high-granularity applications.
We have recently demonstrated that immunization with hepatitis C virus-like particles (HCV-LPs) generated in insect cells can elicit both humoral and cellular immune responses in BALB/c mice. Here, ...we evaluate the immunogenicity of HCV-LPs in HLA2.1 transgenic (AAD) mice in comparison to DNA immunization. HCV-LP immunization elicited a significantly stronger humoral immune response than DNA immunization. HCV-LP-immunized mice also developed stronger HCV-specific cellular immune responses than DNA-immunized mice as determined by using quantitative enzyme-linked immunospot (ELISpot) assay and intracellular cytokine staining. In BALB/c mice, immunization with HCV-LPs resulted in a >5 log10reduction in vaccinia titer when challenged with a recombinant vaccinia expressing the HCV structural proteins (vvHCV.S), as compared to 1 log10decrease in DNA immunization. In HLA2.1 transgenic mice, a 1-2 log10reduction resulted from HCV-LP immunization, whereas no reduction was seen from DNA immunization. Adoptive transfer of lymphocytes from HCV-LP-immunized mice to naive mice provided protection against vvHCV.S challenge, and this transferred immunity can be abrogated by either CD4 or CD8 depletion. Our results suggest that HCV-LPs can induce humoral and cellular immune responses that are protective in a surrogate HCV challenge model and that a strong cellular immunity provided by both CD4 and CD8 effector lymphocytes may be important for protection from HCV infection.
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